• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.276-279
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• 2018

Klinefelter syndrome a genetic disorder with various clinical manifestations. Neurological symptoms, such as seizures, are rarely reported with Klinefelter syndrome, and it response well to anti-epileptic drugs. A 5-month-old boy visited the Inha university hospital due to jerking movements and hiccups. The patient had been diagnosed with Klinefelter syndrome at birth and had a medical history of admission to the neonatal intensive care unit due to opisthotonus and ocular deviation at 26 days of age. The patient's serum testosterone level was decreased and his anti-$M{\ddot{u}}llerian$ hormone level was increased. The brain image examination was normal and the electoencephalography and other blood test results showed no specific findings. However, after admission, the patient recurred generalized tonic-clonic-seizures recurred intermittently even after the administration of antiepileptic drugs. This paper reports a case of non-febrile seizures in a child with Klinefelter syndrome who presented with a refractory course.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.272-275
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• 2018

KBG syndrome is a rare neurodevelopmental disorder characterized by intellectual disability, skeletal anomalies, short stature, craniofacial dysmorphism, and macrodontia. ANKRD11 gene mutation and 16q24.3 microdeletion have been reported to cause KBG syndrome. Here, we report two patients with ANKRD11 mutations who initially presented with neurologic symptoms such as developmental delay and seizures. Patient 1 was a 23-month-old boy who presented with a global developmental delay. Language delay was the most dominant feature. He had hypertelorism, hearing impairment, and behavior problems characterized as hyperactivity. A c.1903_1907delAAACA (p.Lys635GInfsTer26) mutation in ANKRD11 was identified with diagnostic exome sequencing. Patient 2 was a 14-month-old boy with developmental delay and seizure. He also had atrial septum defect, and ventricular septal defect. Generalized tonic seizures began at the age of 8 months. Electroencephalography showed generalized sharp and slow wave pattern. Seizures did not respond to antiepileptic drugs. A loss of function mutation c.5350_5351delTC (p.ser1784HisfsTer12) in ANKRD11 was identified with diagnostic exome sequencing. In both cases, characteristic features of KBG syndrome such as short stature or macrodontia, were absent, and they visited the hospital due to neurological symptoms. These findings suggest that more patients with mild phenotypes of KBG syndrome are being recognized with advances in diagnostic exome sequencing genetic technologies.

• Journal of Environmental Health Sciences
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• v.45 no.3
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• pp.203-212
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• 2019

Objective: A total of five students at same middle school were reported to be diagnosed with pediatric leukemia (n=2), non-Hodgkin's lymphoma (NHL, n=1) and aplastic anemia (n=2) between 2016 and 2017. The aims of this study are to assess exposure to environmental hazardous agents known to be associated with the risk of leukemia and to examine whether the environment of school is associated with the risk leukemia. Method: A total of 11 environmental agents causing childhood leukemia were monitored using international certified method in schools where patients had ever attended. Radon & Thoron detector was used to monitor real-time airborne radon and thoron level ($Bq/m^3$). Clinician interviewed two among nine patients who agreed to participate in this study in order to examine the association of demographic and genetic factors by individually. Leukemia, NHL, and aplastic anemia were grouped into lymphohematopoietic disorder (LHP). Results: Except for airborne radon level, no environmental agents in school and household where patients may be exposed were found to higher than recommended airborne level. Clinical investigation found no individual factors that may be associated with the risk of LHP. Higher airborne radon level than Korea EPA's airborne radon criteria ($148Bq/m^3$) was monitored at most of several after-class room of one elementary school, where two leukemia patients graduated. Significant radon level was not monitored at class-room. Significant exposure to radon of patients was not estimated based on time-activity pattern. Conclusions: Our results have concluded that there have been no environmental factors in school and household environment that may be associated the risk of LHP.

• Journal of Life Science
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• v.28 no.12
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• pp.1536-1544
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• 2018

Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.14 no.2
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• pp.97-101
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• 2018

Lesch-Nyhan syndrome is a rare X-linked recessive genetic disorder. During purine metabolism, the hypoxanthine guanine phosphribosyl transferase (HGPRT) enzyme is deficient causing phosphoribosyl transferase to accumulate and resulting in excessive uric acid. Clinical symptoms include hypercalcemia, choreoathetosis, spasticity, mental retardation, and self-injury to lips, tongue or fingers. This results not only in pain caused by the self-injury but also secondary infection of the wound site and the esthetic damage of the soft tissue defect. Dental treatments include conservative methods using intraoral appliances such as soft mouthguards, fixed lip bumpers, and occlusal guards, and invasive methods such as extraction of all teeth or forming an artificial anterior open bite. We report two cases of Lesch-Nyhan syndrome patients with self-mutilation behavior; one was treated with a preservative method using a soft mouthguard, and the other was treated with extraction of all teeth.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.2
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• pp.99-107
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• 2020

Fibromyalgia is a disorder characterized by the core symptom of chronic widespread pain, along with fatigue, sleep disturbances, mood changes, and cognitive difficulties. The etiology of fibromyalgia involves a combination of biological factors, such as genetic vulnerability, alterations in pain processing and stress response system ; psychological factors, such as anxiety, depression, anger, and perceived stress ; environmental factors, such as infections, febrile diseases, and trauma. Central sensitization, which is amplified in the process of sensory stimulation, has been emphasized as a key etiological factor, as supported by enhanced wind-up, delayed aftersensation, decreased nociceptive flexion reflex threshold and functional imaging studies. Several guidelines recommend that a multimodal approach be used to treat fibromyalgia, including both pharmacological and non-pharmacological treatments, tailored to each individual, and that clinicians should provide an intellectual framework through sufficient education and emphasis on the importance of self-management. The prevalence of mood disorders, anxiety disorders, and other psychiatric problems is 7-9 times higher in patients with fibromyalgia than in the general population ; moreover, the association between fibromyalgia and certain psychopathologies or sleep problems has also been suggested. Since psychiatric problems, with shared vulnerabilities and risk factors, interact with fibromyalgia bidirectionally and also affect the disease course, an integrated management approach is needed to determine the risk of comorbidities.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.48-54
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• 2017

Purpose: Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal-recessive disorder characterized by early-onset hypotonia associated with brain malformations in dystroglycanopathy. Although the wide spectrum of congenital muscular dystrophies causes difficulty in diagnosis, correlating the genotype with the clinical phenotype can help diagnose FCMD. Here, we evaluated the correlation of targeted molecular genetic analysis of FKTN gene mutation with the FCMD phenotype. Methods: This study was conducted retrospectively with 9 subjects. Inclusion criteria included clinical symptoms characterized by early-onset hypotonia with magnetic resonance imaging (MRI) featuring brain malformations. FKTN gene-alteration analysis was performed using various FKTN gene-analysis methods, including sequencing. Results: Among the 9 subjects studied, 4 (44.4%) were male and 5 (55.6%) were female. The median age of onset of the first symptom was 3.1 months. The first symptom was a delayed milestone in 6 cases (66.7%). All 9 subjects (100%) presented with early-onset hypotonia and global delayed development. All subjects presented with cortical malformation in their brain MRIs. Of the 9 subjects, 6 subjects had previously undergone muscle biopsy and 4 cases (4/6; 66.7%) showed dystrophic or myopathic features. Pathogenic mutations causing FCMD were identified in 3 cases. Conclusions: In this study, all 3 subjects with FKTN mutations showed important MRI findings (pachygyria and cerebellar dysplasia). These data suggest that patients with characteristic phenotypes who show pachygyria and cerebellar abnormalities in brain MRIs may have a high probability of being diagnosed with FCMD.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.56-61
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• 2009

Purpose: Preeclampsia is a multifactorial disorder with genetic and environmental components. Recently, the STOX1 gene, identified as a candidate gene for preeclampsia in Dutch women, has been shown to be placentally expressed and subject to imprinting with preferential transmission of the maternal allele. The purpose of this study is to investigate whether there is an association between the STOX1 Y153H variation and preeclampsia in Korean pregnant women. Materials and Methods: This study involved 202 preeclamptic and 204 healthy pregnant women who were genotyped for the Y153H variant of the STOX1 gene using a commercially available SNapShot assay kit and an ABI Prism 3730 DNA Analyzer. Results: There were no significant differences in genotype frequencies of the Y153H variant of the STOX1 gene between preeclamptic patients and normal controls (P>0.05). The H allele frequency of the STOX1 Y153H variation was similar in patients with preeclampsia (87.1%) and in normal controls (86.5%). In addition, multiple logistic regression analysis showed that the YH, HH, and YH/HH genotypes were not associated with an increased risk of preeclampsia when compared to the YY genotype. Conclusion: This is the first study to characterize the Y153H variant of the STOX1 gene in Korean patients with preeclampsia. We found no differences in the genotype and allele frequencies between preeclamptic and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the STOX1 Y153H variation is not associated with the development of preeclampsia in Korean pregnant women.

• Journal of Life Science
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• v.22 no.8
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• pp.1057-1063
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• 2012

Epilepsy is the most prevalent chronic neurological disorder and can be controlled by antiepileptic drugs (AEDs) in up to 70% of patients. We performed an association study between adverse drug reactions and the genetic polymorphisms of CYP2C9, CYP2C19, ABCB1, and SCN1A. The clinical data of 83 epilepsy patients who had received AEDs containing carbamazepine (CBZ) were collected. We extracted genomic DNA from peripheral blood and then genotyped CYP2C9 ($CYP2C9^*2$, $CYP2C9^*3$), CYP2C19 ($CYP2C9^*2$, $CYP2C9^*3$), ABCB1 (C3435T), and SCN1A (IVS5N+5 G>A) using direct sequencing. The allele frequencies of $CYP2C9^*3$, $CYP2C9^*2$, $CYP2C9^*3$, ABCB1 (3435C>T), and SCN1A (IVS5N+5 G>A) were 0.93, 0.72, 0.91, 0.61, and 0.55, respectively. Statistically significant differences were indicated from the data obtained. Patients with SCN1A genotype CC or CT were compared with patients with SCN1A genotype TT while using more than 500mg of carbamazepine. We have associated functional polymorphisms with the dose used in regular clinical practice for Korean epilepsy patients who had received antiepileptic drugs (AEDs) containing carbamazepine. For AEDs, we found that one of the SCN1A genotypes is associated with a 500 mg dose. There was no association found with CNS ADR caused by AEDs.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.2
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• pp.113-121
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• 2007

Hearing loss is a common congenital disorder that is frequently associated with mutations in the Cx26 gene (GJB2). Recently, the mutation analysis of GJB2 has been used in a newborn screening test for the detection of hearing impairment. Population-based studies should be performed before the application of genetic testing for the identification of deaf newborns. In this study, 8 positions of GJB2 mutations-including 35delG, 167delT, 235delC, V27I, V37I, M34T, E114G, and I203T-were analyzed using PCR-direct sequencing in a total of 437 healthy Korean neonates. DNAs from dried blood spots were extracted using a commercial DNA extraction kit. The PCR-amplified products (783 bps) of the GJB2 gene were detected using 2% agarose gel electrophoresis and subjected to direct sequencing. The sequences were compared with those in the GenBank database by using the BLAST program. In this study, 5 GJB2 mutations -including V27I (79G>A), V37I (109G>A), E114G (341A>G), I203T (608T>C), and 235delC- were found. Of the 437 neonate samples, 301 subjects showed GJB2 mutations (68.9%, 301/437). The V27I mutation was found in 271 subjects and was the most frequent (62.0%, 271/437). The E114G, I203T and V37I mutations were shown in 146, 17 and 14 subjects, respectively. The 235delC mutation was found in 1 subject. The E114G mutation was frequently accompanied by the V27I mutation. V27I/E114G (97.2%, 143/147) was the most common double mutation and 3 subjects had the double mutation V27I/I203T. A triple mutation, V27I/E114G/I203T, was found in 1 subject. In conclusion, PCR-direct sequencing is a convenient tool for the rapid detection of GJB2 mutations and this data might provide information for the genetic counseling of the GJB2 gene.